The preoptic area and anterior hypothalamus, PO/AH, are important structures in the regulation of body temperature. Certain PO/AH neurons not only sense changes in their own, central temperature; but in addition, they receive afferent synaptic information regarding peripheral and deep-body temperatures. This integrative neuronal network then communicates with other hypothalamic & brainstem areas to control a host of thermoregulatory responses; these responses include evaporative heat loss (sweating, panting), cutaneous blood flow, shivering (muscle tremor), metabolic endocrines, and various behaviors. Also, the neural control of these responses is dramatically affected by neural disease and lesions, fever-producing pyrogens, drugs, and thermal stress. Previous electrophysiological studies have revealed much about the various types of hypothalamic thermosensitive neurons and the ways in which afferent thermal information is integrated with hypothalamic thermal information. On the other hand, surprisingly little is known about the basis of neuronal thermosensitivity or about the synaptic connections within and between the different hypothalamic areas. To better understand this hypothalamic neuronal network, the proposed research will study its sensory and integrative properties using extracellular and intracellular recordings in both tissue slices and anesthetized animals. The thermosensitive properties of these neurons will be determined during synaptic blockade, thermal & electrical stimulation of synaptic pathways, and perfusion with endogenous factors, such as leukocytic pyrogen. The use of both frontal and horizontal tissue slices will permit a more precise characterization of the synaptic connections both within local neuronal networks as well as between different hypothalamic nuclei.